Recommendations

Investigational disease-modifying OA drugs (DMOADs)

Guideline for the management of knee and hip osteoarthritis
Download PDF
  3. Figures and tables
  4. Provided under licence

Last revised: 01 Jul 2018

This clinical guideline was published in 2018  and is currently being updated.

The information provided may not reflect the most current evidence or best practice.

Pharmacological interventions

Investigational disease-modifying OA drugs (DMOADs)


 

Interleukin-1   knee (IL-1) inhibitors –  Knee and/or hip

Recommendation

We do not recommend offering IL-1 inhibitors for people with knee

Strength of recommendation

Strong against recommendation

Quality of evidence

Low

What is it?

This is a group of agents that block the activity of a pro-inflammatory cytokine, IL-1, which is believed to play a role in inducing cartilage matrix degradation through the up-regulation of proteolytic enzymes.108 The most common IL-1 inhibitors are:

  1. IL-1 receptor antagonist – anakinra
  2. soluble decoy receptor – rilonacept
  3. neutralising monoclonal anti-IL-1β antibody – canakinumab.

In addition, a monoclonal antibody directed against the IL-1 receptor, AMG-108 and a neutralising anti-IL-1α or IL-1β antibody, ABT-981 are currently in clinical trials.

Rationale

Results from a three-arm trial of a single intra-articular injection of anakinra at a dose of 50 mg (n = 34) and 150 mg (n = 67) were available. The mean improvement from baseline at week 12 on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score was not statistically different between the anakinra and placebo groups (Appendix 5 of the Guideline for the management of knee and hip osteoarthritis: Technical document).

A placebo-controlled randomised controlled trial (RCT) of AMG-108, (which is not included in Appendix 5 of the Guideline for the management of knee and hip osteoarthritis: Technical document) found non-statistically significant improvement on WOMAC pain after subcutaneous administration of AMG-108.109
As IL-1 inhibitors require an authority prescription, which cannot be prescribed by general practitioners (GPs), GPs need to work with specialists to get access to these agents. The working group discussed the limitations in current efficacy, safety, access and costs, and considered that IL-1 inhibitors are not a feasible nor cost-effective treatment.
There are currently no trials that have investigated the benefits and safety of IL-1 inhibitors in people with hip OA. Using knee OA data to extrapolate to hip or other OA requires additional caution.

Harms

The percentage of participants reporting adverse events was similar between the placebo and anakinra groups (Appendix 5 of the Guideline for the management of knee and hip osteoarthritis: Technical document). The most common adverse event was arthralgia (10%), with similar rates between anakinra 150 mg and placebo groups, but a lower rate for the anakinra 50 mg group (3%). Headache (10% versus 1%), upper respiratory tract infection (8% versus 1%), back pain (8% versus 3%) and extremity pain (6% versus 0%) occurred more often in the anakinra 150 mg group than in the placebo group. Infections were reported in 10% of participants, more frequently for the anakinra 150 mg group, compared with the anakinra 50 mg or the placebo group.

Anti-nerve growth factor (NGF) – Knee and/or hip

Recommendation

We suggest not offering NGF for people with knee  and/or hip OA.

Strength of recommendation

Conditional against recommendation

Quality of evidence

Moderate

What is it?

NGF is a secretory soluble protein that binds to two different cell surface receptors – 75 kDa neurotrophin receptor (p75NTR) and high-affinity NGF-specific tyrosine kinase receptor (TrkA). It is critical for normal development of sympathetic and sensory neurons that are responsible for nociception and temperature sensation.110
A humanised monoclonal antibody, tanezumab, was developed specifically to inhibit NGF from binding to its receptors on pain-signalling neurons. Fulranumab is a fully humanised recombinant immunoglobulin G2 (IgG2) monoclonal antibody that specifically neutralises the biological actions of human NGF.

Rationale

Results from five trials of tanezumab and one of fasimumab found a statistically significant lower WOMAC pain and  function score, compared with placebos with a pooled standardised mean differences (SMDs) of 0.6 and 0.64 respectively (Appendix 5 of the Guideline for the management of knee and hip osteoarthritis: Technical document). The dosage of tanezumab differed between phase II and phase III studies included in the systematic review. There were two phase II studies of tanezumab (References 3 and 5 in PICO, 2.8.3 – Knee in Appendix 5 of the Guideline for the management of knee and hip osteoarthritis: Technical document) which demonstrated SMD ranging from –0.31 to 0.94 with five different dose groups (10 μg/kg, 25 μg/kg, 50 µg/kg, 100 μg/kg, 200 μg/kg). 109 The other phase III studies evaluated a narrower dose range (2.5 mg, 5 mg, 10 mg), and reported a correspondingly narrower range of SMD from 0.26 to 0.61, all of which are statistically significantly from placebo. In the study of fasinumab, all three doses of fasinumab were associated with significant improvements, compared with placebo in walking knee pain and WOMAC total and subscale scores.
In the included hip studies, statistically significant but less clinically relevant effects were found on WOMAC pain and function scores, with pooled SMDs of 0.33 and 0.4 respectively (Appendix 5 of the Guideline for the management of knee and hip osteoarthritis: Technical document). The study (Reference 3 in PICO, 2.8.3 – Hip in Appendix 5 of the Guideline for the management of knee and hip osteoarthritis: Technical document) evaluated fulranumab with two different dosing frequencies (1 and 3 mg every four weeks; 3, 6 and 10 mg every eight weeks), showing a numerical difference from the active control (oxycodone), although no differentiation was seen between either fulranumab dose and placebo in the same study. The working group discussed that anti-NGF requires off-label prescribing and is expensive, which limited its accessibility and affordability.

Harms

Based on current evidence, the number of adverse events was not significantly different between treatment and placebo groups. Reported adverse events included arthralgia, headache, upper respiratory tract infection and abnormal peripheral sensation (eg paraesthesia, dysesthesia, hyperaesthesia, hypoesthesia). A meta-analysis of tanezumab safety suggested the use of tanezumab plus nonsteroidal anti-inflammatory drug (NSAID) treatment had a higher occurrence of serious adverse events than NSAID alone. 111 A recent adjudication of joint-related adverse events in the tanezumab clinical program reported that the drug was not associated with an increased risk of osteonecrosis, but was associated with an increased risk of rapidly progressive OA, especially in people on higher doses of tanezumab, tanezumab plus NSAIDs, or pre-existing subchondral insufficiency fractures.112

Fibroblast growth factor (FGF) – Knee and/or hip

Recommendation

We do not recommend offering FGF for people with knee and/or hip OA.

Strength of recommendation

Strong against recommendation

Quality of evidence

Very low

What is it?

Sprifermin is a recombinant and truncated version of human FGF-18 that binds to, and specifically activates, FGF receptor-3 in cartilage in order to promote chondrocyte proliferation and cartilage matrix production.

Rationale

There is one trial of 190 participants with knee OA evaluating the effects of intra-articular injection of sprifermin as a single treatment and multiple-dose regimen (three doses of either 10, 30 or 100 μg). Results found that all groups had improved WOMAC pain scores, with statistically significantly less improvement at 12 months in participants receiving the 100 μg dose of sprifermin, compared with participants receiving placebo. No statistically significant relationship between treatment group and reduction in central medial femorotibial compartment cartilage thickness was observed. However, sprifermin was associated with statistically significant, dose-dependent reductions in the loss of total and lateral femorotibial cartilage thickness and volume, and in joint space widening in the lateral femorotibial compartment (Appendix 5 of the Guideline for the management of knee and hip osteoarthritis: Technical document). The reasons for the seemingly preferential effect on the lateral knee compartment in the present and previous studies are not clear. In OA, the status of cartilage differs between the medial and lateral femorotibial compartments, with the medial compartment more commonly severely affected. An anabolic agent acting on cartilage may be less effective in tissue that is severely damaged.
Currently, sprifermin is expensive and mainly available in phase II trials.
No trial has investigated the benefits and safety of sprifermin in people with hip OA. Using knee OA data to extrapolate to hip or other OA requires additional caution.

Harms

According to the findings in two recent trials, the overall proportion of participants experiencing at least one treatmentemergent adverse event (TEAE) was not increased in the sprifermin group, compared with the placebo group (Appendix 5 of the Guideline for the management of knee and hip osteoarthritis: Technical document). Incidence, severity and nature of reported TEAEs raised no local or systemic safety concerns for doses up to 300 μg.113

Colchicine – Knee and/or hip

Recommendation

We suggest not offering colchicine for people with knee and/or hip OA.

Strength of recommendation

Conditional against recommendation

Quality of evidence

Very low

What is it?

Colchicine is a medication most commonly used to treat gout. It is a toxic natural product and secondary metabolite, originally extracted from plants of the genus colchicum. The hypothesis of action of colchicine is that it can block inflammasomemediated inflammatory and biochemical joint degradation. The therapeutic use of colchicine has extended beyond gouty arthritis and familial Mediterranean fever to OA, pericarditis and atherosclerosis.114

Rationale

There is currently a lack of high-quality evidence supporting the use of colchicine for symptomatic relief for people with knee OA. While two small trials (one comparing colchicine to placebo; one comparing the combination of colchicine and an anti-inflammatory medication to the anti-inflammatory medication alone) indicate colchicine may provide symptomatic relief (Appendix 5 of the Guideline for the management of knee and hip osteoarthritis: Technical document), its efficacy and safety remains unproven. In the trials, participants who received colchicine reported more gastrointestinal adverse effects, and the benefit to risk profile needs to be investigated in larger studies. One randomised placebo-controlled trial for people with knee OA that commenced enrolment of 120 participants in June 2014 in Singapore is reported to have been completed (Identifier: NCT02176460; ClinicalTrials.gov), but the results have not been published. One additional trial was identified in a search of the World Health Organization’s (WHO’s) International Clinical Trials Registry Platform (ICTRP). This trial is reported to have recruited 81 participants between March and September 2012 in Iran, and was retrospectively registered in September 2015 (IRCT2015071623240N1). These results have also not been published.
There are currently no trials investigating the benefits and safety of colchicine in people with OA of the hip.
Colchicine currently does not have an indication via the Therapeutic Goods Administration (TGA) for OA, and should be considered as an investigational medication only.

Harms

There was no significant adverse event in the included trials of colchicine. The most commonly reported adverse events encountered with colchicine were gastrointestinal adverse events (eg loose bowel movements, pain in the abdomen), which were usually mild.

Methotrexate – Knee and/or hip

Recommendation

We suggest not offering methotrexate for people with knee  and/or hip OA.

Strength of recommendation

Conditional against recommendation

Quality of evidence

Low

What is it?

Methotrexate is a chemotherapy agent and immune system suppressant, which is commonly used to treat cancer and autoimmune diseases (eg rheumatoid arthritis, psoriasis). For treating inflammatory arthritis, multiple mechanisms appear to be involved, including the inhibition of:

  1. enzymes involved in purine metabolism, leading to accumulation of adenosine
  2. T-cell activation and suppression of intercellular adhesion molecule expression by T-cells
  3. methyltransferase activity, leading to deactivation of enzyme activity relevant to immune system function.

Rationale

There is very low-quality evidence from one small trial of 56 participants who used 7.5 mg of methotrexate weekly versus placebo for painful knee OA, which did not find a reduction in pain at four months (Appendix 5 of the Guideline for the management of knee and hip osteoarthritis: Technical document). Another open-label study evaluated the effects of methotrexate for pain relief in participants with knee OA. At 24 weeks, 13/30 participants (43%) achieved ≥30% reduction in Visual Analogue Scale (VAS) pain, of whom, seven (23%) had achieved ≥50% reduction. Conversely, four participants (13%) experienced a flare. Thirteen of 30 (43%) participants achieved Osteoarthritis Research Society International’s responder criteria.115 An ongoing pragmatic phase III trial (ISRCTN77854383) has been designed to confirm these inconsistent findings. In terms of cost and access, methotrexate is a relatively cheap and widely available. Currently, there is no direct evidence for hip OA.
Methotrexate does not currently have an indication via the TGA for OA, and should be considered as an investigational medication only.

Harms

The side effects of methotrexate can include gastrointestinal side effects, haematological abnormalities and elevated liver transaminases. Side effects resulting in discontinuation of the drug vary in frequency from 15% to 17%, but have been shown to reduce to 4% in the second year of treatment.116,117

  1. Australian Institute of Health and Welfare. AIHW analysis of ABS Microdata: National Health Survey 2014–15. Canberra: AIHW, 2015.
  2. Cross M, Smith E, Hoy D, et al. The global burden of hip and knee osteoarthritis: Estimates from the global burden of disease 2010 study. Ann Rheum Dis 2014;73(7):1323–30.
  3. Kassebaum NJ, Arora M, Barber RM, et al. Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990–2013: A systematic analysis for the Global Burden of Disease Study 2015. Lancet 2015;388(10053):1603–58.
  4. Hunter DJ, Schofield D, Callander E. The individual and socioeconomic impact of osteoarthritis. Nat Rev Rheumatol 2014;10(7):437–41. [Perspective]
  5. Arthritis Australia. Count the Costs and Bank the Savings: The current and future burden of arthritis. Sydney: Arthritis Australia, 2016.
  6. Arthritis Australia. Time to move: Osteoarthritis. Sydney: Arthritis Australia, 2014.
  7. Britt H, Miller G, Henderson J, et al. General practice activity in Australia 2015–16. General practice series no. 40. Sydney: Sydney University Press, 2016.
  8. The Royal Australian College of General Practitioners. Guideline for the non-surgical management of hip and knee osteoarthritis. South Melbourne, VIC: RACGP, 2009.
  9. Mackenbach JP. Socioeconomic inequalities in health in high-income countries: The facts and the options. In: Detels R, Gulliford M, Karim QA, Tan CC, editors. Oxford Textbook of Global Public Health. 6th edn. Oxford: Oxford University Press, 2015.
  10. Brennan-Olsen SL, Cook S, Leech MT, et al. Prevalence of arthritis according to age, sex and socioeconomic status in six low and middle income countries: Analysis of data from the World Health Organization study on global AGEing and adult health (SAGE) Wave 1. BMC Musculoskelet Disord 2017;18(1):271.
  11. Australian Institute of Health and Welfare. Australia’s health 2016. Cat. no. AUS 199. Canberra: AIHW, 2016.
  12. Brimblecombe JK, O’Dea K. The role of energy cost in food choices for an Aboriginal population in northern Australia. Med J Aust 2009;190(10):549–51.
  13. Lo YT, Chang YH, Lee MS, Wahlqvist ML. Health and nutrition economics: Diet costs are associated with diet quality. Asia Pac J Clin Nutr 2009;18(4):598–604.
  14. Sommer I, Griebler U, Mahlknecht P, et al. Socioeconomic inequalities in non-communicable diseases and their risk factors: An overview of systematic reviews. BMC Public Health 2015;15(1):914.
  15. Australian Institute of Health and Welfare. Arthritis and other musculoskeletal conditions. Canberra: AIHW, 2017.
  16. Australian Bureau of Statistics. 4704.0 – The health and welfare of Australia’s Aboriginal and Torres Strait Islander peoples, Oct 2010. Canberra: ABS, 2010.
  17. The Royal Australian College of General Practitioners.
  18. Guidelines for preventive activities in general practice. 9th edn. East Melbourne, VIC: RACGP, 2016.
  19. Abbott P, Reath J, Gordon E, et al. General practitioner supervisor assessment and teaching of registrars consulting with Aboriginal patients – Is cultural competence adequately considered? BMC Med Educ 2014;14(1):167.
  20. Ethnic Communities’ Council of Victoria. An investment not an expense: Enhancing health literacy in culturally and linguistically diverse communities. Carlton, Vic: Ethnic Communities’ Council of Victoria, 2012.
  21. National Institute for Health and Care Excellence.
  22. Osteoarthritis: Care and management. London: NICE, 2014.
  23. Lim AY, Doherty M. What of guidelines for osteoarthritis? Int J Rheum Dis 2011;14(2):136–44.
  24. Turk DC, Rudy TE, Sorkin BA. Neglected topics in chronic pain treatment outcome studies: Determination of success. Pain 1993;53(1):3–16.
  25. Williamson A, Hoggart B. Pain: A review of three commonly used pain rating scales. J Clin Nurs 2005;14(7):798–804.
  26. Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation study of WOMAC:A health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 1988;15(12):1833–40.
  27. Roos EM, Roos HP, Lohmander LS, Ekdahl C, Beynnon BD. Knee Injury and Osteoarthritis Outcome Score (KOOS) – Development of a self-administered outcome measure. J Orthop Sports Phys Ther 1998;28(2):88–96.
  28. Nilsdotter AK, Lohmander LS, Klassbo M, Roos EM. Hip
  29. Disability and Osteoarthritis Outcome Score (HOOS) – Validity and responsiveness in total hip replacement. BMC Musculoskelet Disord 2003;4(1):10.
  30. Dobson F, Hinman RS, Roos EM, et al. OARSI recommended performance-based tests to assess physical function in people diagnosed with hip or knee osteoarthritis. Osteoarthritis Cartilage 2013;21(8):1042–52.
  31. Sakellariou G, Conaghan PG, Zhang W, et al. EULAR recommendations for the use of imaging in the clinical management of peripheral joint osteoarthritis. Ann Rheum Dis 2017;76(9):1484–94.
  32. Altman R, Asch E, Bloch D, et al. Development of criteria for the classification and reporting of osteoarthritis: Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum 1986;29(8):1039–49.
  33. Altman RD, Hochberg M, Murphy WA Jr, Wolfe F, Lequesne M. Atlas of individual radiographic features in osteoarthritis. Osteoarthritis Cartilage 1995;3 Suppl A:3–70.
  34. Zhang W, Doherty M, Peat G, et al. EULAR evidence-based recommendations for the diagnosis of knee osteoarthritis. Ann Rheum Dis 2010;69(3):483–89.
  35. Altman R, Alarcon G, Appelrouth D, et al. The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hip. Arthritis Rheum 1991;34(5):505–14.
  36. Guermazi A, Niu J, Hayashi D, et al. Prevalence of abnormalities in knees detected by MRI in adults without knee osteoarthritis: Population based observational study (Framingham Osteoarthritis Study). BMJ 2012;345:e5339.
  37. Bedson J, Croft PR. The discordance between clinical and radiographic knee osteoarthritis: A systematic search and summary of the literature. BMC Musculoskelet Disord 2008;9:116.
  38. Kim C, Nevitt MC, Niu J, et al. Association of hip pain with radiographic evidence of hip osteoarthritis: Diagnostic test study. BMJ 2015;351:h5983.
  39. Ang DC, Ibrahim SA, Burant CJ, Kwoh CK. Is there a difference in the perception of symptoms between African Americans and whites with osteoarthritis? J Rheumatol 2003;30(6): 1305–10.
  40. Bruyere O, Honore A, Rovati LC, et al. Radiologic features poorly predict clinical outcomes in knee osteoarthritis. Scand J Rheumatol 2002;31(1):13–16.
  41. Lethbridge-Cejku M, Scott WW, Jr, Reichle R, et al. Association of radiographic features of osteoarthritis of the knee with knee pain: Data from the Baltimore Longitudinal Study of Aging. Arthritis Care Res 1995;8(3):182–88.
  42. Bhattacharyya T, Gale D, Dewire P, et al. The clinical importance of meniscal tears demonstrated by magnetic resonance imaging in osteoarthritis of the knee. J Bone Joint Surg Am 2003;85(1):4–9.
  43. Englund M, Guermazi A, Gale D, et al. Incidental meniscal findings on knee MRI in middle-aged and elderly persons. N Engl J Med 2008;359(11):1108–15.
  44. Brand C, Hunter D, Hinman R, March L, Osborne R,
  45. Bennell K. Improving care for people with osteoarthritis of the hip and knee: How has national policy for osteoarthritis been translated into service models in Australia? Int J Rheum Dis 2011;14(2):181–90.
  46. McAlindon TE, Bannuru RR, Sullivan M, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis Cartilage 2014;22(3):363–88.
  47. Kroon FP, van der Burg LR, Buchbinder R, Osborne RH, Johnston RV, Pitt V. Self-management education programmes for osteoarthritis. Cochrane Database Syst Rev 2014;15(1):CD008963.
  48. French SD, Bennell KL, Nicolson PJ, Hodges PW, Dobson FL, Hinman RS. What do people with knee or hip osteoarthritis need to know? An international consensus list of essential statements for osteoarthritis. Arthritis Care Res 2015;67(6):809–16.
  49. Hill J, Bird H. Patient knowledge and misconceptions of osteoarthritis assessed by a validated self-completed knowledge questionnaire (PKQ-OA). Rheumatology (Oxford) 2007;46(5):796–800.
  50. Higashi H, Barendregt JJ. Cost-effectiveness of total hip and knee replacements for the Australian population with osteoarthritis: Discrete-event simulation model. PLoS One 2011;6(9):e25403.
  51. Ruiz Jr D, Koenig L, Dall TM, et al. The direct and indirect costs to society of treatment for end-stage knee osteoarthritis. J Bone Joint Surg Am 2013;95(16):1473–80.
  52. Culliford DJ, Maskell J, Kiran A, et al. The lifetime risk of total hip and knee arthroplasty: Results from the UK general practice research database. Osteoarthritis Cartilage 2012;20(6):519–24.
  53. Cobos R, Latorre A, Aizpuru F, et al. Variability of indication criteria in knee and hip replacement: An observational study. BMC Musculoskelet Disord 2010;11(1):249.
  54. Dowsey M, Nikpour M, Dieppe P, Choong P. Associations between pre-operative radiographic changes and outcomes after total knee joint replacement for osteoarthritis. Osteoarthritis Cartilage 2012;20(10):1095–102.
  55. Dowsey MM, Nikpour M, Dieppe P, Choong PF. Associations between pre-operative radiographic osteoarthritis severity and pain and function after total hip replacement. Clin Rheumatol 2016;35(1):183–89.
  56. Dowsey MM, Spelman T, Choong PF. Development of a prognostic nomogram for predicting the probability of nonresponse to total knee arthroplasty 1 year after surgery. J Arthroplasty 2016;31(8):1654–60.
  57. Kehlet H, Thienpont E. Fast-track knee arthroplasty – Status and future challenges. Knee 2013;20 Suppl 1:S29–33.
  58. Bjorgul K, Novicoff WM, Saleh KJ. Evaluating comorbidities in total hip and knee arthroplasty: Available instruments. J Orthop Traumatol 2010;11(4):203–9.
  59. Ageberg E, Nilsdotter A, Kosek E, Roos EM. Effects of neuromuscular training (NEMEX-TJR) on patient-reported outcomes and physical function in severe primary hip or knee osteoarthritis: A controlled before-and-after study. BMC Musculoskelet Disord 2013;14(1):232.
  60. Villadsen A, Overgaard S, Holsgaard-Larsen A, Christensen R, Roos EM. Immediate efficacy of neuromuscular exercise in patients with severe osteoarthritis of the hip or knee:
  61. A secondary analysis from a randomized controlled trial. J Rheumatol 2014;41(7):1385–94.
  62. Singh JA, Lewallen D. Predictors of pain and use of pain medications following primary Total Hip Arthroplasty (THA): 5,707 THAs at 2-years and 3,289 THAs at 5-years. BMC Musculoskelet Disord 2010;11(1):90.
  63. Wylde V, Hewlett S, Learmonth ID, Dieppe P. Persistent pain after joint replacement: Prevalence, sensory qualities, and postoperative determinants. Pain 2011;152(3):566–72.
  64. Stacey D, Legare F, Lewis K, et al. Decision aids for people facing health treatment or screening decisions. Cochrane Database Syst Rev 2017;4:CD001431.
  65. Elwyn G, O’Connor A, Stacey D, et al. International Patient Decision Aids Standards (IPDAS) collaboration. Developing a quality criteria framework for patient decision aid: Online international Delphi consensus process. BMJ 2006;333(7565):417–19.
  66. de Achaval S, Fraenkel L, Volk RJ, Cox V, Suarez-Almazor ME. Impact of educational and patient decision aids on decisional conflict associated with total knee arthroplasty. Arthritis Care Res 2012;64(2):229–37.
  67. Fraenkel L, Rabidou N, Wittink D, Fried T. Improving informed decision-making for patients with knee pain. J Rheumatol 2007;34(9):1894–98.
  68. Coleman K, Norris S, Weston A, et al. NHMRC additional levels of evidence and grades for recommendations for developers of guidelines. Canberra: NHMRC, 2009.
  69. Higgins JP, Altman DG, Gotzsche PC, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928.
  70. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959;22(4):719–48.
  71. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7(3):177–88.
  72. GRADEpro G. GRADEpro GDT: GRADEpro Guideline
  73. Development Tool [Software]. McMaster University, 2015 (developed by Evidence Prime, Inc.) gradepro.org [Accessed 19 June 2018].
  74. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: An emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336(7650):924–26.
  75. Guyatt GH, Oxman AD, Kunz R, et al. GRADE guidelines 6.
  76. Rating the quality of evidence-imprecision. J Clin Epidemiol 2011;64(12):1283–93.
  77. Guyatt GH, Oxman AD, Kunz R, et al. GRADE guidelines: 8. Rating the quality of evidence – Indirectness. J Clin Epidemiol 2011;64(12):1303–10.
  78. Guyatt GH, Oxman AD, Kunz R, et al. GRADE guidelines: 7. Rating the quality of evidence – Inconsistency. J Clin Epidemiol 2011;64(12):1294–302.
  79. Guyatt GH, Oxman AD, Vist G, et al. GRADE guidelines: 4.
  80. Rating the quality of evidence – Study limitations (risk of bias). J Clin Epidemiol 2011 Apr;64(4):407–15.
  81. Guyatt G, Oxman AD, Sultan S, et al. GRADE guidelines:
  82. Making an overall rating of confidence in effect estimates for a single outcome and for all outcomes. J Clin Epidemiol 2013;66(2):151–57.
  83. Andrews J, Guyatt G, Oxman AD, et al. GRADE guidelines: 14. Going from evidence to recommendations: The significance and presentation of recommendations. J Clin Epidemiol 2013 Jul;66(7):719–25.
  84. Andrews JC, Schunemann HJ, Oxman AD, et al. GRADE guidelines: 15. Going from evidence to recommendationdeterminants of a recommendation’s direction and strength. J Clin Epidemiol 2013;66(7):726–35.
  85. Jaeschke R, Guyatt GH, Dellinger P, et al. Use of GRADE grid to reach decisions on clinical practice guidelines when consensus is elusive. BMJ 2008;337:a744.
  86. O’Moore KA, Newby JM, Andrews G, et al. Internet cognitive behaviour therapy for depression in older adults with knee osteoarthritis: A randomized controlled trial. Arthritis Care Res 2017;70(1):61–70.
  87. Broderick JE, Keefe FJ, Schneider S, et al. Cognitive behavioral therapy for chronic pain is effective, but for whom? Pain 2016;157(9):2115–23.
  88. Dear BF, Gandy M, Karin E, et al. The Pain Course: A randomised controlled trial examining an internet-delivered pain management program when provided with different levels of clinician support. Pain 2015;156(10):1920–35.
  89. Quicke JG, Foster NE, Thomas MJ, Holden MA. Is longterm physical activity safe for older adults with knee pain? A systematic review. Osteoarthritis Cartilage 2015;23(9):1445–56.
  90. Atukorala I, Makovey J, Lawler L, Messier SP, Bennell K, Hunter DJ. Is there a dose-response relationship between weight loss and symptom improvement in persons with knee osteoarthritis? Arthritis Care Res 2016;68(8):1106–14.
  91. Messier SP, Mihalko SL, Legault C, et al. Effects of intensive diet and exercise on knee joint loads, inflammation, and clinical outcomes among overweight and obese adults with knee osteoarthritis: The IDEA randomized clinical trial. JAMA 2013;310(12):1263–73.
  92. National Health and Medical Research Council. Clinical practice guidelines for the management of overweight and obesity in adults, adolescents and children in Australia. Melbourne: NHMRC, 2013.
  93. Queensland Government. Queensland Health 2014: Nutrition education materials online – Using body mass index resources/hphe_usingbmi.pdf [Accessed 25 April 2018].
  94. Hunter GR, Plaisance EP, Fisher G. Weight loss and bone mineral density. Curr Opin Endocrinol Diabetes Obes 2014;21(5):358–62.
  95. Cardoso JS, Riley JL, Glover T, et al. Experimental pain phenotyping in community-dwelling individuals with knee osteoarthritis. Pain 2016;157(9):2104–14.
  96. Moss P, Knight E, Wright A. Subjects with knee osteoarthritis exhibit widespread hyperalgesia to pressure and cold. PLoS One 2016;11(1):e0147526.
  97. Erhart JC, Dyrby CO, D’Lima DD, Colwell CW, Andriacchi TP. Changes in in vivo knee loading with a variable-stiffness intervention shoe correlate with changes in the knee adduction moment. J Orthop Res 2010;28(12):1548–53.
  98. Trombini-Souza F, Kimura A, Ribeiro AP, et al. Inexpensive footwear decreases joint loading in elderly women with knee osteoarthritis. Gait Posture 2011;34(1):126–30.
  99. Bennell KL, Kean CO, Wrigley TV, Hinman RS. Effects of a modified shoe on knee load in people with and those without knee osteoarthritis. Arthritis Rheum 201;65(3):701–9.
  100. Radzimski AO, Mundermann A, Sole G. Effect of footwear on the external knee adduction moment – A systematic review. Knee 2012;19(3):163–75.
  101. Crossley KM, Marino GP, Macilquham MD, Schache AG, Hinman RS. Can patellar tape reduce the patellar malalignment and pain associated with patellofemoral osteoarthritis? Arthritis Rheum 2009;61(12):1719–25.
  102. Hinman RS, Bennell KL, Crossley KM, McConnell J. Immediate effects of adhesive tape on pain and disability in individuals with knee osteoarthritis. Rheumatology 2003;42(7):865–69.
  103. Stelian J, Gil I, Habot B, et al. Improvement of pain and disability in elderly patients with degenerative osteoarthritis of the knee treated with narrow-band light therapy. J Am Geriatr Soc 1992;40(1):23–26.
  104. Machado GC, Maher CG, Ferreira PH, et al. Efficacy and safety of paracetamol for spinal pain and osteoarthritis: Systematic review and meta-analysis of randomised placebo controlled trials. BMJ 2015;350:h1225.
  105. Roberts E, Delgado Nunes V, Buckner S, et al. Paracetamol: Not as safe as we thought? A systematic literature review of observational studies. Ann Rheum Dis 2016;75(3):552–59.
  106. Crofford LJ. Use of NSAIDs in treating patients with arthritis. Arthritis Res Ther 2013;15 Suppl 3(Suppl 3):S2.
  107. Kaplovitch E, Gomes T, Camacho X, Dhalla IA, Mamdani MM, Juurlink DN. Sex differences in dose escalation and overdose death during chronic opioid therapy: A populationbased cohort study. PLoS One 2015;10(8):e0134550.
  108. Vithlani RH, Baranidharan G. Transdermal opioids for cancer pain management. Rev Pain 2010;4(2):8–13.
  109. Simon LS, Grierson LM, Naseer Z, Bookman AA, Zev Shainhouse J. Efficacy and safety of topical diclofenac containing dimethyl sulfoxide (DMSO) compared with those of topical placebo, DMSO vehicle and oral diclofenac for knee osteoarthritis. Pain 2009;143(3):238–45.
  110. Guedes V, Castro JP, Brito I. Topical capsaicin for pain in osteoarthritis: A literature review. Reumatol Clin 2016;14(1):40–45.
  111. Laslett LL, Jones G. Capsaicin for osteoarthritis pain. Prog Drug Res 2014;68:277–91.
  112. Brown JP, Boulay LJ. Clinical experience with duloxetine in the management of chronic musculoskeletal pain. A focus on osteoarthritis of the knee. Ther Adv Musculoskelet Dis 2013;5(6):291–304.
  113. Smith Jr GN, Mickler EA, Hasty KA, Brandt KD. Specificity of inhibition of matrix metalloproteinase activity by doxycycline: Relationship to structure of the enzyme. Arthritis Rheum 1999;42(6):1140–46.
  114. Davis AJ, Smith TO, Hing CB, Sofat N. Are bisphosphonates effective in the treatment of osteoarthritis pain? A metaanalysis and systematic review. PLoS One 2013;8(9):e72714.
  115. Manicourt D, Devogelaer J, Azria M, Silverman S. Rationale for the potential use of calcitonin in osteoarthritis. J Musculoskelet Neuronal Interact 2005;5(3):285–93.
  116. European Medicines Agency. Guideline on clinical investigation of medicinal products used in the treatment of osteoarthritis. London: EMA, 2010.
  117. Dinarello CA, Simon A, van der Meer JW. Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat Rev Drug Discov 2012;11(8):633–52.
  118. Cohen SB, Proudman S, Kivitz AJ, et al. A randomized, double-blind study of AMG 108 (a fully human monoclonal antibody to IL-1R1) in patients with osteoarthritis of the knee. Arthritis Res Ther 2011;13(4):R125.
  119. Lane NE, Corr M. Osteoarthritis in 2016: Anti-NGF treatments for pain – Two steps forward, one step back? Nat Rev Rheumatol 2017;13(2):76–78.
  120. Schnitzer TJ, Marks JA. A systematic review of the efficacy and general safety of antibodies to NGF in the treatment of OA of the hip or knee. Osteoarthritis Cartilage 2015;23 Suppl 1:S8–17.
  121. Hochberg MC, Tive LA, Abramson SB, et al. When is osteonecrosis not osteonecrosis? Adjudication of reported serious adverse joint events in the Tanezumab Clinical Development Program. Arthritis Rheumatol 2016;68(2):382–91.
  122. Dahlberg LE, Aydemir A, Muurahainen N, et al. A first-inhuman, double-blind, randomised, placebo-controlled, dose ascending study of intra-articular rhFGF18 (sprifermin) in patients with advanced knee osteoarthritis. Clin Exp Rheumatol 2016;34(3):445–50.
  123. Leung YY, Yao Hui LL, Kraus VB. Colchicine – Update on mechanisms of action and therapeutic uses. Semin Arthritis Rheum 2015;45(3):341–50.
  124. Wenham CY, Grainger AJ, Hensor EM, Caperon AR, Ash ZR, Conaghan PG. Methotrexate for pain relief in knee osteoarthritis: An open-label study. Rheumatology 2013;52(5):888–92.
  125. Salaffi F, Carotti M, Sartini A, Cervini C. A prospective study of the long-term efficacy and toxicity of low-dose methotrexate in rheumatoid arthritis. Clin Exp Rheumatol 1995;13(1):23–28.
  126. Schnabel A, Herlyn K, Burchardi C, Reinhold-Keller E, Gross
  127. WL. Long-term tolerability of methotrexate at doses exceeding 15 mg per week in rheumatoid arthritis. Rheumatol Int 1996;15(5):195–200.
  128. McAlindon TE, LaValley MP, Harvey WF, et al. Effect of intraarticular triamcinolone vs saline on knee cartilage volume and pain in patients with knee osteoarthritis: A randomized clinical trial. JAMA 2017;317(19):1967–75.
  129. Hunter DJ. Viscosupplementation for osteoarthritis of the knee. N Engl J Med 2015;372(11):1040–47.
  130. Albert C, Brocq O, Gerard D, Roux C, Euller-Ziegler L. Septic knee arthritis after intra-articular hyaluronate injection. Two case reports. Joint Bone Spine 2006;73(2):205–7.
  131. Chang KV, Hung CY, Aliwarga F, Wang TG, Han DS, Chen WS. Comparative effectiveness of platelet-rich plasma injections for treating knee joint cartilage degenerative pathology: A systematic review and meta-analysis. Arch Phys Med Rehabil 2014;95(3):562–75.
  132. Dai WL, Zhou AG, Zhang H, Zhang J. Efficacy of platelet-rich plasma in the treatment of knee osteoarthritis: A meta-analysis of randomized controlled trials. Arthroscopy 2017;33(3):659–70.
  133. Osborne H, Anderson L, Burt P, Young M, Gerrard D.
  134. Australasian College of Sports Physicians position statement: The place of mesenchymal stem/stromal cell therapies in sport and exercise medicine. Br J Sports Med 2016;50(20):1237– 44.
  135. Centeno CJ, Busse D, Kisiday J, Keohan C, Freeman M, Karli D. Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells. Pain Physician 2008;11(3):343–53.
  136. Vega A, Martin-Ferrero MA, Del Canto F, et al. Treatment of knee osteoarthritis with allogeneic bone marrow mesenchymal stem cells: A randomized controlled trial. Transplantation 2015;99(8):1681–90.
  137. Rabago D, Patterson JJ, Mundt M, et al. Dextrose prolotherapy for knee osteoarthritis: A randomized controlled trial. Ann Fam Med 2013;11(3):229–37.
  138. Cameron M, Chrubasik S. Oral herbal therapies for treating osteoarthritis. Cochrane Database Syst Rev 2014;22(5):CD002947.
This event attracts CPD points and can be self recorded

Did you know you can now log your CPD with a click of a button?

Create Quick log

Related documents

  Administrative-report.pdf (PDF 2.76 MB)

  Implementation-plan.pdf (PDF 1.79 MB)

  Technical-document.pdf (PDF 5.79 MB)

Advertising